Low-Dose Aspirin Treatment Attenuates Male Rat Salt-Sensitive Hypertension via Platelet Cyclooxygenase 1 and Complement Cascade Pathway.

Abstract

Background The role of platelets in the development of vascular inflammation and endothelial dysfunction in the pathogenesis of hypertension is well established at this time. Aspirin is known to relieve pain, decrease fever, reduce inflammation, impair platelet aggregation, and prevent clotting, yet its effect in the context of salt-sensitive hypertension remains unclear. The present study investigated the importance of aspirin in inhibiting the abnormal activation of platelets and promoting the normal function of the vascular endothelium in a rat model of salt-sensitive hypertension. Method and Results Dahl salt-sensitive rats and salt-resistant rats were fed a normal-salt diet (4% NaCl), a high-salt diet (8% NaCl), or a high-salt diet with aspirin gavage (10 mg/kg per day) for 8 weeks. Blood pressure, platelet activation, vascular function, inflammatory response, and potential mechanism were measured. Low-dose aspirin (10 mg/kg per day) decreased the high-salt diet-induced elevation of blood pressure, platelet activation, leukocyte infiltration, and leukocyte-platelet aggregation (CD45+CD61+), as well as vascular endothelial and renal damage. These effects were related to the ability of aspirin to prevent the adhesion of leukocytes to endothelial cells via inhibition of the platelet cyclooxygenase 1 but not the cyclooxygenase 2 pathway. Aspirin also reversed the high-salt diet-induced abnormal activation of complement and coagulation cascades in platelets. Conclusions These results highlight a new property of aspirin in ameliorating vascular endothelial dysfunction induced by platelet activation, which may be beneficial in the treatment of salt-sensitive hypertension.

• Authors: Xiaoliang Jiang, Xue Liu, Xing Liu, Xianxian Wu, Pedro A Jose, Min Liu, Zhiwei Yang
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 9 Issue 1 Pg. e013470 (01 07 2020) ISSN: 2047-9980 [Electronic] England
• PMID: 31852420 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclooxygenase Inhibitors
• Membrane Proteins
• Sodium Chloride, Dietary
• Cyclooxygenase 1
• Ptgs1 protein, rat
• Aspirin

Topics

• Animals
• Aspirin (administration & dosage)
• Blood Platelets (drug effects, enzymology)
• Blood Pressure (drug effects)
• Cells, Cultured
• Complement Activation (drug effects)
• Cyclooxygenase 1 (blood)
• Cyclooxygenase Inhibitors (administration & dosage)
• Disease Models, Animal
• Endothelium, Vascular (drug effects, enzymology, physiopathology)
• Humans
• Hypertension (chemically induced, enzymology, physiopathology, prevention & control)
• Male
• Membrane Proteins (antagonists & inhibitors, blood)
• Platelet Activation (drug effects)
• Rats, Inbred Dahl
• Signal Transduction
• Sodium Chloride, Dietary